Gene therapy in mice improves Rett syndrome

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Scientists have used a gene therapy technique to reverse symptoms of Rett syndrome in mice, showing the potential for clinical application.

Rett syndrome, an X-linked autism disorder that primarily occurs in girls, affects one in about 10,000 children a year. Mutations in an X-linked gene called MECP2 (methyl CpG-binding protein) are the culprit behind the disorder, which causes developmental reversals. The MECP2 gene acts as a regulator for many other genes, switching their activity on or off.

"Because MECP2 binds to DNA throughout the genome, there is no single gene currently that we can point to and target with a drug," Gail Mandel, a Howard Hughes investigator at Oregon Health and Sciences University who led the study, explained in a statement. "Therefore the best chance of having a major impact on the disorder is to correct the underlying defect in as many cells throughout the body as possible. Gene therapy allows us to do that."

Researchers took healthy genes and delivered them into cells aboard the adeno-associated virus serotype 9 (AAV9), which has the ability to cross the blood-brain barrier--a characteristic that allows the virus and its cargo to be administered intravenously. But the virus has limited cargo space and can't hold the entire MECP2 gene, so Mandel and his team partnered with researchers at Nationwide Children's Hospital in Columbus, OH, to bundle the gene's most critical segments with the virus.

Researchers injected the virus in mice with a rodent form of Rett syndrome and observed that the virus distributed the modified gene while making its way throughout the body and brain. This induced the production of MECP2 protein. Symptoms associated with Rett syndrome, including motor function, tremors, seizures and hind limb clasping, all improved in the treated mice.

In humans and mice with Rett syndrome, about 50% of the cells have a healthy copy of MECP2. After the mice were treated with the gene therapy, 65% of their cells contained a functioning MECP2 gene.

- here's the study abstract
- read the press release

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